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An open-label expanded access program of afatinib in EGFR tyrosine kinase inhibitor-naïve patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR mutations

BACKGROUND: Afatinib is approved globally for EGFR-TKI treatment-naïve patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). In this Korean expanded access program, we evaluated its ‘real-world’ safety and efficacy. METHODS: EGFR-TKI treatment-naïve patients with EGFR mutation-pos...

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Autores principales: Park, Keunchil, Kim, Jin-Soo, Kim, Joo-Hang, Kim, Young-Chul, Kim, Hoon-Gu, Cho, Eun Kyung, Jin, Jong-Youl, Kim, Miyoung, Märten, Angela, Kang, Jin-Hyoung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274031/
https://www.ncbi.nlm.nih.gov/pubmed/34253172
http://dx.doi.org/10.1186/s12885-021-08445-9
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author Park, Keunchil
Kim, Jin-Soo
Kim, Joo-Hang
Kim, Young-Chul
Kim, Hoon-Gu
Cho, Eun Kyung
Jin, Jong-Youl
Kim, Miyoung
Märten, Angela
Kang, Jin-Hyoung
author_facet Park, Keunchil
Kim, Jin-Soo
Kim, Joo-Hang
Kim, Young-Chul
Kim, Hoon-Gu
Cho, Eun Kyung
Jin, Jong-Youl
Kim, Miyoung
Märten, Angela
Kang, Jin-Hyoung
author_sort Park, Keunchil
collection PubMed
description BACKGROUND: Afatinib is approved globally for EGFR-TKI treatment-naïve patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). In this Korean expanded access program, we evaluated its ‘real-world’ safety and efficacy. METHODS: EGFR-TKI treatment-naïve patients with EGFR mutation-positive NSCLC received afatinib 40 mg/day until disease progression or other withdrawal criteria. Dose reductions were permitted for adverse events (AEs). The primary endpoint was the number of patients with AEs (CTCAE version 3.0). Other endpoints included progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and changes in investigator-assessed cancer-related symptoms. RESULTS: Eighty-eight patients received afatinib, including 27 (31%) with brain metastases and 16 (18%) with uncommon EGFR mutations. Median PFS was 17.0 months (95% confidence interval [CI] 12.9–23.3 months). Grade 3 treatment-related AEs (TRAEs) were reported in 51 (58%) patients; the most common were diarrhea (22%) and rash/acne (20%). No grade > 3 TRAEs were reported. AEs leading to dose reduction occurred in 49 (56%) patients. Treatment discontinuation due to TRAEs occurred in 4 (5%) patients. ORR was 81% overall, 89% in patients with brain metastases, and 55% in patients with uncommon mutations (excluding T790M/exon 20 insertions). Median DOR was 15.1 months (95% CI 12.4–21.4 months). Cancer-related symptoms were improved/unchanged/worsened in 34–66%/36–66%/0–3% of patients over the first year. CONCLUSIONS: No unexpected safety signals for afatinib were observed. AEs were manageable; the treatment discontinuation rate was low. Afatinib showed encouraging efficacy in a broad patient population including those with brain metastases or tumors harboring uncommon EGFR mutations. TRIALS REGISTRATION: ClinicalTrials.gov NCT01931306; 29/08/2013. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08445-9.
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spelling pubmed-82740312021-07-13 An open-label expanded access program of afatinib in EGFR tyrosine kinase inhibitor-naïve patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR mutations Park, Keunchil Kim, Jin-Soo Kim, Joo-Hang Kim, Young-Chul Kim, Hoon-Gu Cho, Eun Kyung Jin, Jong-Youl Kim, Miyoung Märten, Angela Kang, Jin-Hyoung BMC Cancer Research BACKGROUND: Afatinib is approved globally for EGFR-TKI treatment-naïve patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). In this Korean expanded access program, we evaluated its ‘real-world’ safety and efficacy. METHODS: EGFR-TKI treatment-naïve patients with EGFR mutation-positive NSCLC received afatinib 40 mg/day until disease progression or other withdrawal criteria. Dose reductions were permitted for adverse events (AEs). The primary endpoint was the number of patients with AEs (CTCAE version 3.0). Other endpoints included progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and changes in investigator-assessed cancer-related symptoms. RESULTS: Eighty-eight patients received afatinib, including 27 (31%) with brain metastases and 16 (18%) with uncommon EGFR mutations. Median PFS was 17.0 months (95% confidence interval [CI] 12.9–23.3 months). Grade 3 treatment-related AEs (TRAEs) were reported in 51 (58%) patients; the most common were diarrhea (22%) and rash/acne (20%). No grade > 3 TRAEs were reported. AEs leading to dose reduction occurred in 49 (56%) patients. Treatment discontinuation due to TRAEs occurred in 4 (5%) patients. ORR was 81% overall, 89% in patients with brain metastases, and 55% in patients with uncommon mutations (excluding T790M/exon 20 insertions). Median DOR was 15.1 months (95% CI 12.4–21.4 months). Cancer-related symptoms were improved/unchanged/worsened in 34–66%/36–66%/0–3% of patients over the first year. CONCLUSIONS: No unexpected safety signals for afatinib were observed. AEs were manageable; the treatment discontinuation rate was low. Afatinib showed encouraging efficacy in a broad patient population including those with brain metastases or tumors harboring uncommon EGFR mutations. TRIALS REGISTRATION: ClinicalTrials.gov NCT01931306; 29/08/2013. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08445-9. BioMed Central 2021-07-12 /pmc/articles/PMC8274031/ /pubmed/34253172 http://dx.doi.org/10.1186/s12885-021-08445-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Park, Keunchil
Kim, Jin-Soo
Kim, Joo-Hang
Kim, Young-Chul
Kim, Hoon-Gu
Cho, Eun Kyung
Jin, Jong-Youl
Kim, Miyoung
Märten, Angela
Kang, Jin-Hyoung
An open-label expanded access program of afatinib in EGFR tyrosine kinase inhibitor-naïve patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR mutations
title An open-label expanded access program of afatinib in EGFR tyrosine kinase inhibitor-naïve patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR mutations
title_full An open-label expanded access program of afatinib in EGFR tyrosine kinase inhibitor-naïve patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR mutations
title_fullStr An open-label expanded access program of afatinib in EGFR tyrosine kinase inhibitor-naïve patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR mutations
title_full_unstemmed An open-label expanded access program of afatinib in EGFR tyrosine kinase inhibitor-naïve patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR mutations
title_short An open-label expanded access program of afatinib in EGFR tyrosine kinase inhibitor-naïve patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR mutations
title_sort open-label expanded access program of afatinib in egfr tyrosine kinase inhibitor-naïve patients with locally advanced or metastatic non-small cell lung cancer harboring egfr mutations
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274031/
https://www.ncbi.nlm.nih.gov/pubmed/34253172
http://dx.doi.org/10.1186/s12885-021-08445-9
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